The objective of this research proposal is to eventually be able to make a clear-cut distinction between benign and malignant lymphoreticular infiltrates that occur in the conjunctiva, orbit and other ocular tissues. These tumors constitute a significant clinical and pathologic problem, in that up to a third of them cannot be adequately diagnosed by conventional light microscopy. The systematic serial study of freshly obtained biopsy specimens processed for in vitro immunologic studies, immunohistochemistry, electron microscopy and immunoelectron microscopy will allow for correlative cytologic, immunologic and ultrastructural characterization of these lymphoreticular infiltrates. In particular, the application of direct immunoperoxidase techniques to the detection of lymphocyte markers in formalin fixed paraffin embedded tissue, will permit correlation of tissue sections with in vitro immunologic studies. Thus, it will be possible to correlate the topographic orientation and interrelationships in tissue section of the various cell populations characterized more fully by in vitro immunologic studies. Furthermore, the IP staining of paraffin embedded material of over 400 file cases with known follow-ups will serve to test the conclusions derived from the prospective investigations. It is proposed that a polyclonal cellular composition will typify benign infiltrates, whereas monoclonal infiltrates will be discovered in malignant lesions. Information derived from these studies after evaluation may become the cornerstone in diagnosis and prognosis of patients with ocular reticular lesions as well as a determining factor in therapy.